1. Field of the Invention
The present invention relates, in general, to diagnostic kits for the measurement of a fluid sample characteristic and, in particular, to diagnostic kits that include test strip calibration codes and related methods.
2. Description of the Related Art
Typical diagnostic kits for the measurement of a fluid sample characteristic include a device, such as a hand-held meter, and a test strip (e.g., a disposable blood glucose test strip) to which a fluid sample is applied. The device and test strip are used in tandem to measure an analyte concentration(s) (e.g., blood glucose concentration) or other characteristic(s) (e.g., prothrombin time [PT] and/or International Normalization Ratio [INR]) of the fluid sample. The device typically measures a property or properties of the test strip (e.g., an optical reflectance, optical transmittance or an electrochemical property) and then employs an algorithm(s) to calculate the characteristic based on the measured property or properties. Such conventional diagnostic kits are described in, for example, U.S. Pat. No. 6,084,660, issued on Jul. 4, 2000 and U.S. Pat. No. 6,261,519, issued Jul. 17, 2001 and U.S. patent application Ser. No. 10/100,531, filed Mar. 14, 2002, each of which is hereby fully incorporated by reference, as well as PCT patent applications WO 0248707 A2 and WO 0157510 A2.
In order to account for lot-to-lot variation in the test strips of such diagnostic kits, it is commonplace for test strip lots to be calibrated during their manufacture. Such calibration typically includes the determination of calibration parameters and the assignment of a test strip calibration code, associated with those calibration parameters, to each of the test strip lots. For example, in order to assign a test strip calibration code to a lot of prothrombin test strips, coagulation and PT calibration parameters can be experimentally determined using orthogonal regression routines. In such orthogonal regression routines, the bias between experimental test results and reference test results is minimized using a sum of squares function by adjusting various calibration parameters. The result of such an orthogonal regression routine is a set of experimental calibration parameters. If these calibration coefficients were assigned as calibration codes, there would be infinite number of calibration codes. In order to make a finite and manageable number of calibration codes, the experimental calibration parameters are then shifted to coincide with the closest calibration parameters contained in a pre-defined calibration parameter table. A calibration code associated with the closest calibration parameters is subsequently assigned to the lot of prothrombin test strips.
Conventional techniques of assigning test strip calibration codes to a lot of test strips, such as the calibration technique described above with respect to prothrombin test strips, have the drawbacks of (i) employing a sum of squares function, which is unduly sensitive to extreme experimental results and (ii) assuming that the calibration parameters from the predefined calibration parameter table that are closest to the experimentally determined calibration parameters are the most optimal, which is not necessarily correct. Due to these drawbacks, the accuracy of results obtained using a diagnostic kit that employs test strip calibration codes that have been associated with calibration parameters (and therefore associated with test strip lots) using conventional techniques may not be optimal.
In addition, under certain circumstances, it can be desirable to re-calibrate a test strip lot to verify the previous assignment of a test strip calibration code thereto. However, if individual test strip calibration codes are associated with calibration parameters that are too closely spaced (i.e., calibration parameters separated by a small increment of resolution), it is possible that a test strip lot will be assigned a test strip calibration code upon recalibration that is different from the test strip calibration code previously assigned. This can occur since, even though the recalibration was performed correctly, a finite calibration error is associated with the recalibration. The possible inconsistency of assigning a different test strip calibration code upon recalibration complicates verification of the assignment of a test strip calibration code to a test strip lot.
When a diagnostic kit is used to measure a characteristic of a fluid sample, the test strip calibration code assigned to the test strip enables the device to obtain calibration parameters for use in calculating the characteristic. There are several techniques that can be employed to convey the test strip calibration code assigned to a test strip to the device. These techniques include using a button on the device to select a numeric test strip calibration code; insertion into the device of an integrated circuit with a test strip calibration code; insertion into the device of a strip with a test strip calibration code that employs passive electronic components (e.g., resistors); proximal telemetry; and the use of a bar code or Read Only Memory (ROM) integrated circuit (see, for example, U.S. Pat. No. 5,489,414, U.S. Pat. No. 5,366,609 and European Patent 0880407 B1). In general, the simplest and most inexpensive technique is for a user to convey a test strip calibration code to a device by depressing a calibration code button on the device. However, in order for this technique to be practical, it is desirable that the device employs a minimal number of test strip calibration codes (e.g., one hundred or less test strip calibration codes, and more preferably 50 or less test strip calibration codes). Otherwise, conveying the test strip calibration code to the device is cumbersome for the user and the likelihood of user error is unduly high. On the other hand, there must be a sufficient number of test strip calibration codes to maintain the overall accuracy of the diagnostic kit.
Still needed in the field, therefore, is diagnostic kit that enables the use of a minimal number of test strip calibration codes and that employs test strip calibration codes that are optimally associated with calibration parameters and, thus, also optimally associated with test strip lots. Also needed, therefore, is a method for optimally associating test strip calibration codes to calibration parameters.
The present invention provides a diagnostic kit that includes test strip calibration codes that are optimally associated with calibration parameters and that, therefore, enables the use of a minimal number of test strip calibration codes. Since the test strip calibration codes are optimally associated with the calibration parameters, the test strip calibration codes will also be optimally assigned to a test strip lot during test strip calibration.
In arriving at the present invention, it was recognized that each test strip calibration code represents a geometric region of a multi-dimensional calibration parameter space (e.g., a two-dimensional calibration parameter space). It was further recognized that the multi-dimensional calibration parameter space consists of several non-overlapping geometric regions each associated with a unique calibration code. It was also recognized that this distribution of calibration codes associated with each geometric region and the calibration code assignment introduces a xe2x80x9cquantization errorxe2x80x9d that should be optimally reduced. Such a quantization error can also be viewed as the error that is introduced into a diagnostic kit""s performance by assigning a test strip calibration code to a test strip that is not coincident with the measured calibration coefficients. It was additionally recognized that quantization error should not add considerable amount to the testing error associated with measuring the calibration coefficients.
It was also recognized that distributing the test strip calibration parameters and geometric regions across the multi-dimensional calibration parameter space such that the quantization error is optimally reduced to the extent of testing error in measuring the calibration coefficients provides the most efficient arrangement. Such an efficient arrangement enables the use of a minimal number of test strip calibration codes and an optimal association of test strip calibration codes to calibration parameters. In addition, by minimizing overlap through understanding the uncertainty in measuring the calibration parameters due to testing error, the possibility of assigning a different test strip calibration code to a particular test strip lot during re-calibration is also minimized. This can occur since the geometric region associated with each calibration code can represent an area equivalent to that covered by the uncertainty in measuring the calibration codes.
It was further recognized that the increment of resolution between test strip calibration codes and the boundary of the geometric region represented by a test strip calibration code define the number of test strip calibration codes within the multi-dimensional calibration parameter space. This increment of resolution can, for example, be limited at the upper end by a diagnostic kit""s overall accuracy requirements. If the increment of resolution is too large, the quantization error attributed to the assignment of test strip calibration codes to calibration parameters is undesirably large. However, when the increment of resolution is too small (e.g., when calibration error is larger than the increment of resolution), an unnecessarily large number of calibration codes results and recalibration inconsistency can occur.
For the reasons discussed above, diagnostic kits according to the present invention include test strip calibration codes and geometric regions that have been optimally distributed across a multi-dimensional calibration parameter space. Such optimization involves properly defining an increment of resolution for the test strip calibration codes and the shape (e.g., boundary) of the geometric region represented by each test strip calibration code in order to optimally reduce quantization error while minimizing the number of test strip calibration codes. Examples of suitable geometric regions are hexagons, parallelograms, rectangles, and other like polygonal structures.
A diagnostic kit for measuring a characteristic of a fluid sample according to an exemplary embodiment of the present invention includes a test strip and device (such as a hand-held meter) for measuring a property or properties (e.g., an optical or electrochemical property) of the test strip. The device also calculates a characteristic (e.g., PT and INR) of a fluid sample applied to the test strip, based on the measured property or properties of the test strip.
The device includes a memory with a plurality of test strip calibration codes stored therein. Each of the plurality of test strip calibration codes stored in the memory represents a geometric region of a multi-dimensional calibration parameter space. In addition, the plurality of test strip calibration codes and geometric regions are distributed across the multi-dimensional calibration parameter space such that a quantization error of assigning one of the plurality of test strip calibration codes to the test strip is optimally reduced.
The optimal reduction of the quantization error can include, for example, optimizing the distribution of test strip calibration codes and the shape of the geometric region represented by each test strip calibration code such that a minimum number of test strip calibration codes are stored in the memory while maintaining predetermined quantization error limits. The predetermined quantization error limits employed during optimization can, for example, be based on overall diagnostic kit accuracy requirements and an assessment of testing error in measuring the calibration coefficients. For example, the quantization error limits can be based on a fraction (e.g., one fifth or one twentieth) of the overall diagnostic kit accuracy requirements.
Since the test strip calibration codes and geometric regions are distributed based on optimally reducing the quantization error and in a manner directly related to accuracy requirements, calibration parameters are not necessarily associated with their closest test strip calibration code. This is beneficial since, depending on the diagnostic kit, diagnostic kit performance accuracy can be optimized by not assigning the closest neighboring test strip calibration parameter as particular combinations of calibration parameters can have a self-compensating effect.
Also provided by the present invention is a method for optimally associating test strip calibration codes to calibration parameters for use in a diagnostic kit that includes a test strip and a device with a memory. The method includes optimally distributing a plurality of test strip calibration codes, and geometric regions represented thereby, across a calibration parameter space such that a quantization error of assigning one of the plurality of test strip calibration codes to the test strip is optimally reduced. The plurality of test strip calibration codes that have been thus distributed are then stored in a memory of the diagnostic kit.